Exercise for Depression: A Feasibility Trial Exploring Neural Mechanisms

Objective: The aim of this study was to test the feasibility of an exercise augmentation to pharmacotherapy in depressed younger and older adults while exploring neural mechanisms. Methods: A randomized, double-blind, controlled clinical trial was conducted in 15 inactive younger (20–39 years)and older (60–79 years)adults meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a major depressive episode (https://clinicaltrials.gov/ct2/show/NCT02407704). Participants were randomized to receive a 12-week regimen of venlafaxine XR or venlafaxine XR plus supervised exercise. Cardiorespiratory fitness was assessed using a submaximal VO ₂ test, and neuroimaging assessments were conducted using a Siemans MAGNETOM 7-Tesla magnetic resonance scanner at the University of Pittsburgh. Results: Attrition was 38% and 14% for the medication and exercise groups, respectively. Attendance was 91% for the exercise intervention. Exploratory analyses revealed an association between improvement in fitness and increased cortical thickness in the anterior cingulate cortex. Conclusion: Exercise augmentation to pharmacotherapy is feasible for depressed younger and older adults and may have neural benefits in a core brain region implicated in depression.